Significant gray matter (GM) deficits have been well documented in normal aging and in a variety of neuropsychiatric disorders including schizophrenia and Alzheimer's Disease (white matter (WM) changes are typically much less significant). While these deficits have been quantified, the underlying mechanisms for the volumetric reductions are not clearly understood and likely differ for different pathologies. In this study, we investigated in vivo spectroscopic measurements of GM/WM NAA ratios to help characterize the morphological changes observed in normal aging and other psychiatric disorders. Methods Due to folding of the thin cortical GM ribbon with WM, spectroscopic voxels, even on the order of icc, invariably contain a significant mixture of both tissue types. We developed a linear regression model for computing pure gray matter and pure white matter NAA signal levels. This method is based on combining high-resolution segmented CSF/gray matter/white matter MRI anatomical images with spectroscopic imaging data. To study the effect of aging, spectroscopic imaging studies were performed on five young (20-28 yr.), five older (65-79 yr.) healthy control subjects. With partial volume corrections, the older subjectts data demonstrates a significant reduction (p <.03) in the GM/WM NAA ratios. This is consistent with a neurodegenerative process. The schizophrenic subjects demonstrated GM/WM NAA ratios consistent with a failure of proper neuronal development rather than neurodegeneration. Results and Discussion Investigators have reported varying gray and white matter NAA levels with both aging and neuropsychiatric disorders. These studies have not been performed with precise GM/WM partial volume corrections. Our studies suggest that carefully addressing this issue leads to improved measurement of pure GM and WM NAA levels. These data may be very valuable in elucidating mechanisms of gray matter loss.